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1.
The toxicity of heavy metals such as mercury (Hg) in humans and animals is well documented. The kidney is the primary deposition site of inorganic-Hg and target organ of its toxicity. The present study investigated the protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside (SDG) on nephrotoxicity induced by mercuric chloride (HgCl2). Rats were intraperitoneally injected with HgCl2 (2 mg/kg/day) and renal toxicity was induced. Subcutaneous administration of rats with SDG (5 mg/kg/day) as a pre-treatment caused a significant reversal of HgCl2 induced increase in blood urea, creatinine, glutathione s-transferase and catalase (CAT). On the other hand, administration of SDG with HgCl2 restored normal levels of albumin and superoxide dismutase (SOD). Histological examination of kidneys confirmed that pre-treatment of SDG before HgCl2 administration significantly reduced its pathological effects. Thus, the results of the present investigation suggest that SDG can significantly reduce renal damage, serum and tissue biochemical profiles caused by HgCl2 induced nephrotoxicity. Hence, SDG may be recommended for clinical trials in the treatment of kidney disorders caused by exposure to Hg. 相似文献
2.
Summary Studies were conducted to evaluate the uptake of mercury by wheat ( Triticum aestivum L. runar) and beans ( Phaseolus vulgaris L. marshal) growth on an oxisol with different levels of 2-methoxyethylmercury chloride (Aretan) and mercuric chloride. Dry matter and grain yields of wheat were little affected by either Aretan or mercuric chloride, although Aretan at 50 mg Hg/kg soil delayed germination by four to five days. Germination of beans grown with both compounds at the 50 mg Hg/kg soil failed completely, even after repeated sowing. Yields were somewhat, though not significantly, decreased by mercury chloride up to 5 mg Hg/kg soil.The concentration of Hg in wheat straw and grain increased significantly with increased levels of Aretan and HgCl 2 application, with more Hg taken up by the plants grown with HgCl 2 than with those grown with Aretan. Translocation of Hg to grain was greater in the plants grown with HgCl 2.The concentration of Hg in bean straw, but not grain, increased significantly with increasing levels of Aretan and HgCl 2 application, and was greater in plants grown with HgCl 2. Translocation to grain was low, with little difference between plants grown with Aretan or HgCl 2. 相似文献
3.
Parenteral administration of mercuric chloride (HgCl 2) to rats enhanced lipid peroxidation in liver, kidney, lung, testis, and serum (but not in heart, spleen, or muscle), as
measured by the thiobarbituric acid reaction for malondialdehyde (MDA) in fresh tissue homogenates and body fluids. After
sc injection of HgCl 2 (5 mg/kg body wt), MDA concentrations in liver and kidney became significantly increased by 9 h and reached peak values at
24 h. Dose-response studies were carried out with male albino rats of the Fisher-344 strain (body wt 170–280 g) injected with
1, 3, 5 mg Hg/kg as HgCl 2 and sacrificed after 24 h. In time-response studies, animals were administered 5 mg Hg/kg as HgCl 2 and sacrificed after 3, 9, 18, 24, and 48 h. Studies in the authors' laboratory have shown that (1) concentrations of MDA
are increased in targets (liver, kidney, lung, and testis) of HgCl 2-treated rats; (2) severity of hepatotoxicity and nephrotoxicity is generally consistent with the elevation of Hg and MDA
concentrations, based upon the time-course and dose-effect relationships observed after administration of HgCl 2 to rats; and (3) concentrations of MDA are reduced in target tissues after pretreatment with antioxidants and chelators to
HgCl 2-treated rats. The results of this study implicate that the lipid peroxidation is one of the molecular mechanisms for cell
injury in acute HgCl 2 poisoning. 相似文献
4.
Acute effects of mercuric chloride (HgCl 2) were evaluated on mice. Mice received a single dose of HgCl 2 (4.6 mg/kg, subcutaneously) for three consecutive days. Thirty minutes after the last injection with HgCl 2, mice received one single injection of 2,3-dimercapto-1-propanesulfonic acid (DMPS) or N-acetylcysteine (NAC) or diphenyl diselenide (PhSe) 2. DMPS, NAC and (PhSe) 2 were utilized as therapy against mercury exposure. At 24 h after the last HgCl 2 injection, blood, liver and kidney samples were collected. δ-Aminolevulinate dehydratase (δ-ALA-D) and Na +, K -+ ATPase activities, thiobarbituric acid-reactive substances (TBARS), non-protein thiols (NPSH) and ascorbic acid concentrations
were evaluated. Plasma aspartate (AST) and alanine (ALT) aminotransferase activities, as well as urea and creatinine levels
were determined. The group of mice exposed to Hg + (PhSe) 2 presented 100% of lethality. Exposure with HgCl 2 caused a decrease on the body weight gain and treatments did not modify this parameter. δ-ALA-D, AST and ALT activities,
TBARS, ascorbic acid levels and NPSH (hepatic and erythrocytic) levels were not changed after HgCl 2 exposure. HgCl 2 caused an increase in renal NPSH content and therapies did not modify these levels. Mice treated with (PhSe) 2, Hg + NAC and Hg + DMPS presented a reduction in plasma NPSH levels. Creatinine and urea levels were increased in mice exposed
to Hg + NAC, while Hg + DMPS group presented an increase only in urea level. Na +, K -+ ATPase activity was inhibited in mice exposed to Hg + DMPS and Hg + NAC. In conclusion, therapies with (PhSe) 2, DMPS and NAC following mercury exposure must be better studied because the formation of more toxic complexes with mercury,
which can mainly damage renal tissue. 相似文献
5.
The interaction of the VO 2+ cation with meso-2,3-dimercaptosuccinic acid (DMSA) was investigated by electron absorption spectroscopy in aqueous solution at different
pH values. The spectral behavior, complemented with a spectrophotometric titration, shows the generation of a [VO(DMSA) 2] 2− complex in which the oxocation interacts with two pairs of deprotonated-SH groups of the acid. It was also found that DMSA
rapidly reduces VO 3
− to VO 2+, which might be chelated by an excess of the acid. DMSA can also produce the partial reduction of a V 2O 5 suspension at pH=5.2. The results of this study suggest that DMSA might be a potentially useful detoxification agent for
vanadium. 相似文献
6.
Mercuric chloride (HgCl 2) disturbs the collagen metabolism in the body which is reflected by altered hydroxyproline fractions in the serum. The aim of the present investigation was to study the effect of HgCl 2 treatment on various hydroxyproline (Hyp) fractions in rat serum and the effect of 2,3-dimercapto-1-propane sulfonic acid (DMPS) treatment on serum Hyp fractions in HgCl 2 treated rats. Other parameters studied included body weight, food intake, water intake and kidney weight. Doses of HgCl 2 used were 0.1, 0.5, 1.0, 2.0, 3.0 mg/kg body weight and that of DMPS was 100 mg DMPS/kg body weight. All the doses of HgCl 2 used caused significant ( p < 0.01) alterations in free, peptide-bound and protein-bound Hyp in the serum when compared with control rats but a dose of 2 mg/kg body weight caused significant ( p < 0.001) alteration even in the total serum Hyp when compared to control rats. Administration of DMPS prior HgCl 2 treatment of rats sacrificed 24 h after the treatment caused a significant decrease of 52% ( p < 0.01) in free Hyp when compared to similar HgCl 2 treated rats. DMPS treatment with HgCl 2 also caused an increase of 61% ( p < 0.001) and 114% ( p < 0. 001) in peptide- and protein-bound Hyp respectively, when compared to HgCl 2 treated rats sacrificed 24 h after mercuric chloride and DMPS treatment. Administration of DMPS followed by HgCl 2 to rats which were sacrificed 48 h later caused no significant change in the total and free Hyp when compared to HgCl 2 treated rats which were sacrificed 48 h after the treatment. But there was a significant decrease of 40% ( p < 0.001) in peptide-bound Hyp and an increase in of 77% ( p < 0.001) in protein-bound Hyp when compared to HgCl 2 treated rats sacrificed 48 h after the treatment. The present study shows that HgCl 2 treatment caused significant alterations in serum Hyp fractions reflecting disturbed composition of connective tissues which were not reversed by DMPS treatment. (Mol Cell Biochem 271: 159–165, 2005) 相似文献
7.
This study evaluated the effects of HgCl 2 on renal parameters in nonlactating and lactating rats and their pups, as well as the preventive role of ZnCl 2. Rats received 27 mg kg ?1 ZnCl 2 for five consecutive days and 5 mg kg ?1 HgCl 2 for five subsequent days (s.c.). A decrease in δ‐aminolevulinic acid dehydratase ( δ‐ALA‐D) activity in the blood and an increase in urine protein content in renal weight as well as in blood and urine Hg levels were observed in lactating and nonlactating rats from Sal―Hg and Zn―Hg groups. ZnCl 2 prevented partially the δ‐ALA‐D inhibition and the proteinuria in nonlactating rats. Renal Hg levels were increased in all HgCl 2 groups, and the ZnCl 2 exposure potentiated this effect in lactating rats. Nonlactating rats exposed to HgCl 2 exhibited an increase in plasma urea and creatinine levels, δ‐ALA‐D activity inhibition and histopathological alterations (necrosis, atrophic tubules and collagen deposition) in the kidneys. ZnCl 2 exposure prevented the biochemical alterations. Hg‐exposed pups showed lower body and renal weight and an increase in the renal Hg levels. In conclusion, mercury‐induced nephrotoxicity differs considerably between lactating and nonlactating rats. Moreover, prior exposure with ZnCl 2 may provide protection to individuals who get exposed to mercury occupationally or accidentally. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
8.
Acute effects of mercury on mouse blood, kidneys, and liver were evaluated. Mice received a single dose of mercuric chloride
(HgCl 2, 4.6 mg/kg, subcutaneously) for three consecutive days. We investigated the possible beneficial effects of antioxidant therapy
( N-acetylcysteine (NAC) and diphenyl diselenide (PhSe) 2) compared with the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), an effective chelating agent in HgCl 2 exposure in mice. We also verified whether metallothionein (MT) induction might be involved in a possible mechanism of protection
against HgCl 2 poisoning and whether different treatments would modify MT levels and other toxicological parameters. The results demonstrated
that HgCl 2 exposure significantly inhibited δ-aminolevulinate dehydratase (δ-ALA-D) activity in liver and only DMPS treatment prevented
the inhibitory effect. Mercuric chloride caused an increase in renal non-protein thiol groups (NPSH) and none of the treatments
modified renal NPSH levels. Urea concentration was increased after HgCl 2 exposure. NAC plus (PhSe) 2 was partially effective in protecting against the effects of mercury. DMPS and (PhSe) 2 were effective in restoring the increment in urea concentration caused by mercury. Thiobarbituric acid-reactive substances
(TBARS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities and ascorbic acid levels were not
modified after mercury exposure. Mercuric chloride poisoning caused an increase in hepatic and renal MT levels and antioxidant
treatments did not modify this parameter. Our data indicated a lack of therapeutic effect of the antioxidants tested. 相似文献
9.
This work investigated the preventive effect of diphenyl diselenide [(PhSe) 2] on renal and hepatic toxicity biomarkers and oxidative parameters in adult mice exposed to mercury chloride (HgCl 2). Selenium (Se) and mercury (Hg) determination was also carried out. Mice received a daily oral dose of (PhSe) 2 (5.0 mg/kg/day) or canola oil for five consecutive days. During the following five days, the animals were treated with a daily subcutaneous dose of HgCl 2 (5.0 mg/kg/day) or saline (0.9%). Twenty-four hours after the last HgCl 2 administration, the animals were sacrificed and biological material was obtained. Concerning toxicity biomarkers, Hg exposure inhibited blood δ-aminolevulinic acid dehydratase (δ-ALA-D), serum alanine aminotransferase (ALT) activity and also increased serum creatinine levels. (PhSe) 2 partially prevented blood δ-ALA-D inhibition and totally prevented the serum creatinine increase. Regarding the oxidative parameters, Hg decreased kidney TBARS levels and increased kidney non-protein thiol levels, while (PhSe) 2 pre-treatment partially protected the kidney thiol levels increase. Animals exposed to HgCl 2 presented Hg content accumulation in blood, kidney and liver. The (PhSe) 2 pre-treatment increased Hg accumulation in kidney and decreased in blood. These results show that (PhSe) 2 can be efficient in protecting against these toxic effects presented by this Hg exposure model. 相似文献
10.
2,3 dimercaptopropanol (BAL), is a dithiol chelating agent, used for the treatment of heavy metal intoxication; however, this compound has low therapeutic efficacy and in some situations may cause neurotoxic effects. In experimental models, administration of high doses of BAL produces seizures that culminate in animal death. However, investigations on the modulation of neurotransmitter system(s) involved in BAL-induced seizures are still lacking in the literature. In the present study, the neurotoxicity of BAL, as measured by the manifestation of seizures was examined and the modulation of glutamatergic and GABAergic receptors and ion channels potentially involved in BAL-induced seizures was investigated. The results demonstrated that BAL (18.6 mg/kg) induced seizures and all mice died within one day. GABAergic allosteric modulators (3 or 12 mg/kg diazepam and 50 mg/kg phenobarbital) blocked the appearance of seizure and reduced almost completely the death caused by BAL. Carbamazepine (5 mg/kg) significantly reduced the incidence of BAL-induced seizures, while sodium valproate and MK-801 were not effective in reducing the incidence of seizures. Valproate (300 mg/kg) and MK-801(0.5 mg/kg) prolonged the latencies for onset of seizures; however, all animals died within one day after BAL administration. High doses of ZnCl 2 (135 mg/kg) blocked the appearance of seizures episodes, but no animal survived more than one day. The content of total non-protein—SH in brain of mice treated with 18.6 and 124 mg/kg BAL increased from 0.9 ± 0.3 nmol/g (control animals) to 1.7 ± 0.3 and 3.5 ± 0.8 nmol/g, respectively. In vitro, 0.1–1 mM concentrations of BAL inhibited [ 3H]glutamate and [ 3H]MK-801 binding, but increased the binding of [ 3H]muscimol to brain synaptic plasma membrane. The results reported here demonstrate that GABAergic allosteric modulators (diazepam and phenobarbital) and carbamazepine, a compound that acts by prolonging the recovery of voltage-activated ion channels from inactivation, are able to abolish BAL-induced seizures, while the NMDA antagonist (MK-801) prolonged the latencies for onset of seizures suggesting that modulators of this subtype of glutamate receptor have a modest role on BAL-induced seizures. The results of the present study suggest that allosteric modulators of GABAergic system and carbamazepine, a voltage-gated Na +-channel antagonist, should be considered for the treatment of animals or patients intoxicated with BAL. 相似文献
11.
This study investigated the ability of zinc (Zn) and N-acetylcysteine (NAC) in preventing the biochemical alterations caused by mercury (Hg) and the retention of this metal in different organs. Adult female rats received ZnCl 2 (27 mg/kg) and/or NAC (5 mg/kg) or saline (0.9%) subcutaneously and after 24 h they received HgCl 2 (5 mg/kg) or saline (0.9%). Twenty-four hours after, they were sacrificed and analyses were performed. Hg inhibited hepatic, renal, and blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, decreased renal total thiol levels, as well as increased serum creatinine and urea levels and aspartate aminotransferase activity. HgCl 2-exposed groups presented an important retention of Hg in all the tissues analyzed. All pre-treatments demonstrated tendency in preventing hepatic δ-ALA-D inhibition, whereas only ZnCl 2 showed this effect on blood enzyme. Moreover, the combination of these compounds completely prevented liver and blood Hg retention. The exposure to Zn and Hg increased hepatic metallothionein levels. These results show that Zn and NAC presented promising effects against the toxicity caused by HgCl 2. 相似文献
12.
This study investigated if lactating and nonlactating rats presented differences in relation to hepatic sensitivity to HgCl 2 and the potential preventive role of ZnCl 2. Lactating (days 3–12 of lactation) and nonlactating rats received 27 mg/kg ZnCl 2 for five consecutive days and 5 mg/kg HgCl 2 for five subsequent days. Lactating and nonlactating rats exposed to HgCl 2 presented a decrease in food intake, a decrease in plasma alanine aminotransferase (ALT), and an increase in hepatic Hg levels when compared to the control group. Only lactating rats exposed to HgCl 2 presented an increase in hepatic δ-aminolevulinic acid dehydratase activity. On the other hand, only nonlactating rats exposed to HgCl 2 presented an increase in plasma aspartate aminotransferase (AST). ZnCl 2 pre-exposure partially protected the increase in plasma AST activity presented by nonlactating rats and potentiated the liver Hg accumulation in lactating rats. Pups from the Sal–Hg and Zn–Hg groups showed a decrease in absolute liver weight and an increase in liver Hg levels. Summarizing, this study demonstrated that lactating rats presented distinct biochemical responses compared to nonlactating rats exposed to HgCl 2 when hepatic parameters were evaluated. 相似文献
13.
Mercury (Hg) is an occupational and environmental contaminant that is a well-recognized health hazard. To approach the concrete
mechanisms of mercury nephrotoxicity and find out a new way to prevent it, the rats were subcutaneously injected with different
dosages of mercuric chloride (HgCl 2)—0, 2.2, 4.4, and 8.8 μmol/kg. The levels of Hg, blood urea nitrogen (BUN), urine protein, glutathione (GSH), malondialdehyde
(MDA) and activities of N-acetyl-beta- d-glucosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione
peroxidase (GSH-Px) were investigated, and the levels of reactive oxygen species (ROS) and apoptosis and the pathological
changes were also observed. In addition, the effects of 1 mmol/kg tea polyphenols (TP) and 0.04 mmol/kg schisandrin B (Sch
B) were studied at 8.8 μmol/kg HgCl 2. It was observed that the levels of Hg, BUN, urine protein, GSH, and MDA and activities of NAG, ALP, and LDH increased significantly;
the activities of SOD and GSH-Px decreased significantly; the levels of ROS and apoptosis increased obviously; and many pathological
changes occurred dose-dependently in the HgCl 2 injection groups. Further investigation indicated that pretreatment with TP and Sch B significantly reversed the toxic effects
of HgCl 2. These results suggested that TP and Sch B might antagonize the nephrotoxicity caused by HgCl 2 exposure. 相似文献
14.
The levels of cyclic 2,3-diphosphoglycerate (cDPG) in methanogenic bacteria are governed by the antagonistic activities of cDPG synthetase and cDPG hydrolase. In this paper we focus on the synthetase from Methanobacterium thermoautotrophicum. The cytoplasmic 150 kDa enzyme catalyzed cDPG synthesis from 2,3-diphosphoglycerate (apparent K m=21 mM), Mg 2+ (K m=3.1 mM) and ATP (K m=1–2 mM). In batch-fed cultures, the enzyme was constitutively present (6–6.5 nmol per min per mg protein) during the different growth phases. In continuous cultures, activity decreased in response to phosphate limitation. The synthetase reaction proceeded with maximal rate at pH 6 and at 65° C and was specifically dependent on high (>0.3M) K + concentrations. The reaction conditions remarkably contrasted to those of cDPG degradation catalyzed by the previously described membrane-bound cDPG hydrolase.Abbreviations
cDPG
Cyclic 2,3-diphosphoglycerate
-
2,3-DPG
2,3-Diphosphoglycerate
-
2-PG
2-Phosphoglycerate
-
3-PG
3-Phosphoglycerate 相似文献
15.
To evaluate the protective potential of lycopene (Lyc) and proanthocyanidins (PCs) against mercuric chloride (HgCl 2)-induced hepatotoxicity, the study focused on the mechanism of oxidative stress. Firstly, the rats were subcutaneously (s.c.)
injected with 0, 2.2, 4.4, and 8.8 μmol/kg HgCl 2. Additionally, 40 mg/kg Lyc and 450 mg/kg PCs were given to the rats intragastrically (i.g.) before exposure to 8.8 μmol/kg
HgCl 2. Then, body weight, liver weight coefficient, mercury (Hg) contents, histological feature, ultrastructure, apoptosis, reactive
oxygen species (ROS), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde
(MDA) in the liver were measured. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) in serum were determined. After
exposure to different concentrations of HgCl 2,it was found that Hg contents, pathological and ultrastructure injury, activities of LDH and ALT, apoptosis, and levels of
ROS, GSH, and MDA increased and the activities of SOD and GSH-Px decreased in a concentration-dependent manner. Further investigation
found that pretreatment with Lyc and PCs inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity.
We concluded that Lyc and PCs had hepatoprotective effects on HgCl 2-induced toxicity by antagonizing oxidative stress in rat liver. 相似文献
16.
The widespread use of sodium nitrite (NaNO 2) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO 2 is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO 2-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO 2 at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO 2 induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO 2-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO 2-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity. 相似文献
17.
We have examined the effects of mercuric chloride on renal glomerular structure. Isolated glomeruli from mercury-treated rats (HgCl 2, 5 mg/kg body wt, s.c.) 1 hour post injection presented a diminished cross-sectional area as compared with control glomeruli [control (μm 2) = 26,310 ± 2,545, HgCl 2 (μm 2) = 18,474 ± 1,828] and higher glomerular calcium content (control = 23 ± 6 nmoles/mg prot, HgCl 2 = 43 ± 7 nmoles/mg prot). Renal sections prepared for immunohistochemical and histochemical analysis showed larger deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl 2-treated rats. Moreover, mieloperoxidase activity measured in isolated glomeruli were also increased as compared with control preparations [MPO (U/mg prot): control = 59 ± 7, HgCl 2 = 134 ± 10]. When the animals were studied 24 hours post HgCl 2 injection, glomerular cross-sectional area values were not different from control values (25,276 ± 1,983 μm 2), while calcium contents were higher than values observed 1 hour after treatment (92 ± 9 nmoles/mg prot). A similar pattern was observed in fibronectin deposits. Hypercellularity in glomerular structures and the higher mieloperoxidase levels were maintained at this time (MPO HgCl 2-rats 24 h = 148 ± 31 U/mg prot). The effects observed in this study are consistent with an inflammatory response in the glomerular structure of HgCl 2-treated rats that could explain the altered renal function described in previous reports in our laboratory. © 1997 John Wiley & Sons, Inc. 相似文献
18.
An-Gong-Niu-Huang Wan (AGNH) is a famous traditional Chinese medicine used for brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As 4S 4) and 10% cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the safety of AGNH is of concern. To address this question, the acute toxicity of AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO 2) and mercuric chloride (HgCl 2). Mice were administrated orally AGNH at 1, 3 and 6 g/kg. AGNH at 3 g/kg contains 2.8 mmol As/kg as realgar and 1.18 mmol Hg/kg as cinnabar. Realgar, cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl 2 (0.256 mmol/kg, 20% of cinnabar) were orally given to mice for comparison. Blood and tissues were collected 8 h later for toxicity evaluation. Serum alanine aminotransferase was increased by arsenite and blood urea nitrogen was increased by HgCl 2. Total As accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much higher than that after realgar. The accumulation of Hg after HgCl 2 in liver was 400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology showed moderate liver and kidney injuries after arsenite and HgCl 2, but injuries were mild or absent after AGNH, realgar, and cinnabar. The expression of metallothionein-1, a biomarker of metal exposure, was increased 4–10-fold by arsenite and HgCl 2, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH, realgar and cinnabar are much less toxic acutely than arsenite and HgCl 2. The chemical forms of As and Hg are extremely important factors in determining their disposition and toxicity. 相似文献
19.
In order to test the effectiveness of complexing therapy on methyl mercury induced neurotoxicity, female rats were treated for five days with either 2,3-dimercaptopropanol (BAL) or D-penicillamine (DPA) beginning 1 or 12 days after the final dose of methyl mercury hydroxide (MMOH). MMOH was administered orally at a dose of 13.3 mg/kg once each day for 3 successive days. BAL, dissolved in peanut oil, was administered sc in a dose of 30 mg/kg twice each treatment day. DPA was dissolved in water and administered sc in a dose of 1200 mg/kg once each treatment day. Therapy begun 1 day after the last MMOH administration was prior to the appearance of toxic signs but therapy begun 12 days later was after signs had developed. The ability of BAL or DPA therapy to alter the distribution of radio-labelled ( 203Hg) MMOH was determined. Both DPA and BAL significantly reduced tissue concentrations of mercury when administered beginning 1 day after MMOH, but only DPA was effective in removing mercury from tissues when treatment was begun 12 days after the last dose of MMOH. In a separate experiment when either BAL or DPA therapy was initiated as above 1 day after the last dose of MMOH, the appearance of neurological signs of toxicity was prevented and weight loss was reversed. When therapy was initiated the twelfh day after the last MMOH dose, neither BAL nor DPA was effective in reversing either neurotoxic signs or weight loss. Therefore, therapy is ineffective in reversing neurological signs if it is delayed too long after MMOH administration, even though it is effective in reducing tissue mercury levels. 相似文献
20.
Ca 2+ is involved in the regulation of a variety of physiological processes, but a persistent increase in free cytosolic Ca 2+ concentrations may contribute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecular mechanism responsible for the BAL toxicity is poorly known. In the present study, the effect of BAL and inorganic and organic mercury on Ca 2+ transport by Ca 2+-ATPases located in the sarco/endoplasmic reticulum of fast-skeletal muscle and brain was examined. Ca 2+ uptake by brain and fast-skeletal muscle microsomes was inhibited in a dose-dependent manner by Hg 2+. The calculated IC 50 for Ca 2+ uptake inhibition by HgCl 2 was 1.05 ± 0.09 M (n = 8) for brain and 0.72 ± 0.06 M (n = 9) for muscle. The difference was significant at p < 0.01 (data expressed as mean ± SD). At a low concentration (1 M), 2,3-dimercaptopropanol had no effect on Ca 2+ uptake by brain or muscle vesicles and did not abolish the inhibition caused by Hg 2+. A high concentration of BAL (1 mM) nearly abolished the inhibition caused by 1.75 M HgCl 2 or 6 M CH 3HgCl in skeletal muscle. Surprisingly, at intermediate concentrations (40–100 M) BAL partially inhibited Ca 2+ transport in brain but had no effect on muscle. Furthermore, ATP hydrolysis by brain or muscle microsomes was not inhibited by BAL. These results suggest that in brain microsomes BAL affects in a different way Ca 2+ transport and ATP hydrolysis. The increase in BAL concentration observed after toxic administration of this compound to experimental animals may contribute to deregulate Ca 2+ homoeostasis and, consequently, to the neurotoxicity of BAL. 相似文献
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